special topics

1. M R S S A M I R A A A B D U L L A H I
Tropical diseases

2. Introduction
 Some of the organisms that cause tropical diseases
are bacteria and viruses, terms that may be familiar to
most people since these types of organisms cause illness
 many familiar viral and bacterial diseases are spread
directly from person to person, by airborne routes of
transmission or by sexual contact.
 Alternatively, some tropical disease agents are
transmitted by an intermediate carrier or vector. The
insect or other invertebrate vector picks up the pathogen
from an infected person or animal and transmits it to
others in the process of feeding

3. viruses
 Viruses are minute infectious agents that generally
consist only of genetic material covered by a protein
shell. They only replicate within cells, which provide
the synthetic machinery necessary to produce new
virus particles.

4. Yellow fever
 Yellow fever is a mosquito-borne viral hemorrhagic fever
with a high case-fatality rate. Clinical manifestations
include hepatic dysfunction, renal failure.
 The yellow fever virus belongs to the
genus, Flavivirus. Flavivirus species are characterized by
having a positive-sense, single-stranded RNA of about
10,000 to 11,000 bases
 The genome codes or three structural proteins: capsid
protein (C), membrane protein M (prM), and envelope
protein (E). It also codes for seven nonstructural protein
molecules

5. .
 It makes use of an arthropod as vector. In particular,
it utilizes mosquitoes, for its transmission to another
host.

6.  The virus replicates in the lymph node.
 The viruses are capable of infecting the dendritic cells. They
may also invade the host’s liver and infect the hepatocytes.
 Liver damage causes the yellowing of the skin (jaundice) of
the host.
 This is the reason this condition is called yellow fever. When
the viral infection leads to significant liver damage, the
disease could become severe and life-threatening to the host.
The disease is formerly called black vomit.
 It is because bleeding in the mouth, the eyes, and the
gastrointestinal tract may result in a vomit containing blood.

7. Ebola
 Ebola virus causes fever, severe headache, backache,
vomiting, diarrhea, and severe hemorrhaging.
 The method by which Ebola is transmitted in nature,
and what animal is its natural host, remains unclear.
 Ebola virus (EBOV) is a member of
the Filoviridae family and causes severe
hemorrhagic fever in humans and nonhuman
primates,

8.  Virus entry and attachment is mediated by a single
envelope glycoprotein (GP) as a class I fusion
protein, which is proteolytically processed during
maturation into two subunits, GP1 and GP2. The GP1
N terminus contains a putative receptor-binding
domain (RBD) and the GP2 C terminus contains a
fusion peptide .GP1 and GP2 are linked by a disulfide
bond (Cys53-Cys609)

9.  EBOV GP is also extensively glycosylated, especially
within a region of GP which contains multiple N- and
O-linked glycans. ebolaviruses primarily target
antigen-presenting cells such as dendritic cells and
macrophages, which are one of the main components
of the innate immune system.

10.  By stander apoptosis of lymphocytes is also
observed, and the induction of adaptive immunity is
also impaired by a significant reduction in their
numbers .Lymphocytes themselves are insensitive to
ebolaviruses and marburgviruses, suggesting that
direct infection of lymphocytes may not be the
cause.

12. lasa
 Lassa virus (LASV) belongs to the family of Arenaviridae.
It is the causative agent of Lassa fever, a potentially fatal
viral hemorrhagic fever in humans for which only limited
treatment options and no licensed vaccine are available
 LASV was first isolated in 1969 from a missionary nurse
who worked in a clinic in a small town, Lassa, in
northeastern Nigeria
 The virus particle consists of only four structural proteins
and a lipid envelope as well as a segmented single-
stranded RNA genome in negative orientation. LASV
replicates in the cytoplasm of the host cell..

13.  The genome consists of a small (s) and a large (l)
RNA fragment of 3.4 and 7 kilobases, respectively.
The small RNA (sRNA) fragment encodes the viral
structural proteins like glycoprotein, precursor
protein, and the nucleoprotein. The large RNA
fragment on its own encodes for nonstructural
proteins including viral polymerase and a small zinc-
binding (Z) protein

14.  It is transmitted by rodents. Symptoms of Lassa
fever include sharp backache and/or headache, sore
throat, fever, rashes, dehydration, general swelling,
skin hemorrhaging, irregular heart beat, and
disorientation.

15. Bacteria
 Bacteria (singular = bacterium) are more complex
than viruses, containing genetic information and
much of the equipment necessary to produce energy
and replicate independently.
 Some bacteria, however, can only reproduce when
growing inside a cell, from which they derive
required nutrients

16. Cholera
 Cholera is a diarrheal disease caused by infection
with Vibrio cholerae, a bacterium most often found
in contaminated water and shellfish, which produces
a toxin that upsets the biochemical balance of cells
lining the intestine and makes them secrete copious
amounts of water and electrolytes.

17.  Cholera Toxin(CT) is made up of two types of
subunits. The larger A subunit (240 amino acids;) is
located centrally, while the five B subunits (103
amino acids; each; are located peripherally.

18.  Cholera toxin, by acting as a classical A-B type toxin,
leads to ADP-ribosylation of G protein, and constitutive
activation of AC(adenylatecyclase enzyme) , thereby
giving rise to increased levels of cyclic AMP within the
host cell . As a result, electrolyte imbalance occurs due to
a rapid efflux of chloride ions and decreased influx of
sodium ions, leading to massive water efflux through the
intestinal cells, thereby causing severe diarrhoea and
vomiting, the cardinal clinical signs of cholera.
Diarrhoea, if untreated, leads to severe dehydration,
electrolyte abnormalities and metabolic acidosis15,
almost inevitably resulting in death.

20. Tuberculosis
 Caused primarily by the bacterium Mycobacterium
tuberculos.this is an infection that can last a lifetime,
resulting in disease to virtually every organ in the
body but primarily affecting the lungs. Tuberculosis
occurs all over the world.
 It is treatable and preventable. Several factors like
human immunodeficiency virus (HIV) co-infection
and other may affect outcome if not properly
addressed

21.  TB was associated with biochemical changes namely
low serum sodium, low serum albumin, low/high
serum calcium, low/high serum potassium, among
others

22.  lungs are more commonly affected by tuberculosis
than any other organ, partly because inhalation is
the commonest mode of infection and partly because
lung tissue provides a favorable environment for the
growth of the organism
 globulin formation increases in the body as a result
of increased immune response where antibodies are
produced.

23. Parasites

Parasites are organisms that live within or on
another organism, the host, at whose expense they
obtain some advantage such as nourishment. This
group of pathogens includes the protozoa (single-
celled organisms more complex than bacteria) and
the helminths(multicellular organisms commonly
referred to as worms).

24. malaria
Over 300 million people develop clinical cases of
malaria each year, and one to three million of them
die. Many of these are children living in Sub-Saharan
Africa.
 Almost half of the world's population lives in an area
where they are at risk of contracting the disease.
Malaria is caused by protozoa of genus Plasmodium.

25.  the parasites are transmitted to humans by female
anopheline mosquitoes. When the mosquito takes a
blood meal on the host, she injects the parasites along
with her saliva. The parasites develop first in liver cells
and then infect red blood cells (erythrocytes), where they
consume hemoglobin, the oxygen-carrying component of
the blood.
 The parasites divide in the red cell, and at the completion
of development the red cell ruptures releasing parasites
that can infect many other erythrocytes. The typical
symptoms of malaria, cycles of chills, fever and sweating,
are experienced by patients at these times.

26.  Parasites also became resistant to the widely used
drug chloroquine and other antimalarials.
 Part of the complex life cycle of the malaria
parasite Plasmodium Falciparum involves invasion
and occupation of a red blood cell. There it
catabolizes hemoglobin in its digestive vacuole in
order to grow and asexually multiply into a new
generation of parasites that can subsequently invade
new healthy red blood cells.

27.  A byproduct of the degraded hemoglobin is heme, a
porphyrin ring with a central iron (Fe) atom, which
is precipitated into hemozoin crystals consisting of
dimers of the heme molecule. Monomers of heme in
solution in the digestive vacuole cytosol would be
toxic to the parasite as they are highly reactive, but in
form of hemozoin crystals the heme is harmless4.
Obvious targets for drug design would be
impedement either of hemozoin crystal growth, or of
the protein assisted dimerization of heme6, 7.

28.  The folate pathway of Plasmodium falciparum is a
well-established malaria drug target with proven
benefits in treatment and prophylaxis These
antifolate compounds target two different enzymes
in the folate pathway of P. falciparum, with
pyrimethamine and sulphadoxine inhibiting
dihydrofolate reductase (DHFR) and
dihydropteroate synthase (DHPS)

29.  The inhibition of the folate pathway cuts down the
amount of folate derivatives that act as one-carbon
carriers in nucleotide synthesis and amino acid
metabolism.
 The malaria parasites became resistant to antifolates by
gaining mutations at the dhfr and dhps genes .
 The changes decrease the binding affinity of the drugs
to the targeted enzyme.
 The interest in antifolates has been renewed in recent
years with the development of new lead compounds and
the novel applications in malaria treatment

30. Trypanosomiasis
 Trypanosomiasis
The protozoa causing trypanosomiasis are closely
related to leishmania parasites. In humans, different
species of the genus Trypanosoma are responsible
for diseases

31.  Unlike malaria and leishmaniasis, the parasites are not
injected during feeding; rather they are deposited by
defecating bugs. The parasite enters the host through the
eyes, nose or mouth, or through breaks in the skin.
Symptoms may appear as acute disease shortly after
infection or as chronic disease years later.
 Acute disease involves fever, swelling of the lymph nodes
and, sometimes, inflammation of the heart muscle and of
the brain. Although the acute stage may be fatal,
especially in children, most infected individuals survive.
 One quarter or more will develop cardiac damage that
may result in heart failure and sudden